JP2019517307A - Method of assembling button of drug delivery device and button of drug delivery device - Google Patents

Abstract

A button (70) for setting the dose of drug and dispensing it from the drug delivery device (1), comprising a plastic component (130) and a metal component (131), wherein the plastic composition The element (130) is at least partially received by the metal component (131) and the metal component (131) is configured to be manipulated by the user to set and dispense a dose. 70). Furthermore, a method of assembly of the button (70) of the drug delivery device (1) and a drug delivery device (1) comprising the button (70) are described.

Description

  The present disclosure relates to a button of a drug delivery device. More particularly, the present disclosure relates to a drug delivery device including a button and a method of assembling the button of the drug delivery device.

  Drug delivery devices, in particular pen-type drug delivery devices, are applied when regular injections are performed by persons who do not have formal medical training. This is becoming increasingly common among diabetic patients, and self-care enables such patients to make effective management of their diabetes. In fact, such drug delivery devices allow the user to dispense several user variable or fixed doses of medication.

  There are basically two types of drug delivery devices: resettable (i.e. reusable) devices, and non-resettable (i.e. disposable) devices. For example, disposable drug delivery devices do not have removable pre-filled cartridges.

  An object of the present disclosure is to provide a button of a drug delivery device and thus a drug delivery device having improved properties. For example, the purpose is to provide a particularly robust, light weight and / or cost effective button. This object is achieved by the subject matter of the independent claims. Further features are the subject matter of the dependent claims.

  According to one aspect, a button of a drug delivery device is provided. This button is adapted to be used as a button or dial grip on the device. The button is applied to setting the dose of the drug and dispensing from the device after being assembled into the device.

As used herein, the term "drug" preferably refers to a pharmaceutical formulation comprising at least one pharmaceutically active compound,
Here, in one embodiment, the pharmaceutically active compound has a molecular weight of up to 1500 Da and / or peptides, proteins, polysaccharides, vaccines, DNA, RNA, enzymes, antibodies or fragments thereof, hormones Or an oligonucleotide, or a mixture of pharmaceutically active compounds as described above,
Here, in a further embodiment, the pharmaceutically active compound is a diabetes or a diabetes related complication such as diabetic retinopathy, thromboembolism such as deep vein thromboembolism or pulmonary thromboembolism, acute coronary syndrome (ACS), useful for the treatment and / or prevention of angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis,
Here, in a further embodiment, the pharmaceutically active compound comprises at least one peptide for the treatment and / or prevention of complications associated with diabetes, such as diabetes or diabetic retinopathy,
Here, in a further embodiment, the pharmaceutically active compound is at least one human insulin or human insulin analogue or derivative, glucagon-like peptide (GLP-1) or analogue or derivative thereof, or exendin-3 or exendin 4 or analogs or derivatives of exendin-3 or exendin-4.

  The insulin analogues may be, for example, Gly (A21), Arg (B31), Arg (B32) human insulin; Lys (B3), Glu (B29) human insulin; Lys (B28), Pro (B29) human insulin; B28) Human insulin; human insulin in which the proline at position B28 is replaced with Asp, Lys, Leu, Val, or Ala, and in position B29, Lys may be replaced by Pro; Ala (B26) human insulin; Des (B28-B30) human insulin; Des (B27) human insulin, and Des (B30) human insulin.

  The insulin derivative is, for example, B29-N-myristoyl-des (B30) human insulin; B29-N-palmitoyl-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29 LysB30 human insulin; B30-N-palmitoyl-ThrB29 LysB30 human insulin; -Des (B30) human insulin; B29-N- (N- lithoclyl- gamma glutamyl)-des (B30) human insulin; B29-N- (ω- Carboxymethyl hepta decanoyl) -des (B30) human insulin, and B29-N- (ω- Karubokishiheputa - decanoyl) human insulin.

  Exendin-4 is, for example, H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gin-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu Exendin-4 (1-39) which is a peptide of Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Pro-Ser-Ger-Ala-Pro-Pro-Pro-Ser-NH2 sequence Means).

The exendin-4 derivatives are, for example, compounds of the following list:
H- (Lys) 4-desPro36, desPro37 Exendin-4 (1-39) -NH2,
H- (Lys) 5-desPro36, desPro37 Exendin-4 (1-39) -NH2,
desPro 36 exendin-4 (1-39),
desPro 36 [Asp 28] exendin-4 (1-39),
desPro 36 [IsoAsp 28] exendin-4 (1-39),
desPro 36 [Met (O) 14, Asp28] Exendin-4 (1-39),
desPro 36 [Met (O) 14, IsoAsp28] Exendin-(1-39),
desPro36 [Trp (O2) 25, Asp28] Exendin-4 (1-39),
desPro 36 [Trp (O2) 25, IsoAsp28] Exendin-4 (1-39),
desPro 36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39),
desPro36 [Met (O) 14Trp (O2) 25, IsoAsp28] Exendin-4 (1-39); or desPro36 [Asp28] Exendin-4 (1-39),
desPro 36 [IsoAsp 28] exendin-4 (1-39),
desPro 36 [Met (O) 14, Asp28] Exendin-4 (1-39),
desPro 36 [Met (O) 14, IsoAsp28] Exendin-(1-39),
desPro36 [Trp (O2) 25, Asp28] Exendin-4 (1-39),
desPro 36 [Trp (O2) 25, IsoAsp28] Exendin-4 (1-39),
desPro 36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39),
desPro 36 [Met (O) 14, Trp (O2) 25, IsoAsp28] Exendin-4 (1-39),
(Wherein the group -Lys6-NH2 may be attached to the C-terminus of the exendin-4 derivative);

Alternatively, an exendin-4 derivative of the following sequence:
desPro 36 exendin-4 (1-39)-Lys 6-NH2 (AVE 0010),
H- (Lys) 6-desPro36 [Asp28] Exendin-4 (1-39) -Lys6-NH2,
desAsp 28 Pro 36, Pro 37, Pro 38 Exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro38 [Asp28] Exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36 [Trp (O2) 25, Asp28] Exendin-4 (1-39) -Lys6-NH2,
H-desAsp28Pro36, Pro37, Pro38 [Trp (O2) 25] Exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36 [Met (O) 14, Asp28] Exendin-4 (1-39) -Lys6-NH2,
desMet (O) 14, Asp28Pro36, Pro37, Pro38 Exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39) -NH2;
desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H-Lys6-desPro36 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -Lys6-NH2,
H-desAsp28, Pro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25] Exendin-4 (1-39) -NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Asp28] Exendin-4 (1-39) -NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39) -NH2,
desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2,
H- (Lys) 6-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (S1-39)-(Lys) 6-NH2,
H-Asn- (Glu) 5-desPro36, Pro37, Pro38 [Met (O) 14, Trp (O2) 25, Asp28] Exendin-4 (1-39)-(Lys) 6-NH2;
Or selected from pharmaceutically acceptable salts or solvates of any one of the exendin-4 derivatives described above.

  For example, hormones such as gonadotropin (follitropin, lutropin, coriongonadotropin, menotropin), somatropin (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, goserelin, etc., Rote Liste, 2008 Pituitary hormones or hypothalamic hormones or regulatory active peptides listed in the above and their antagonists.

  Examples of polysaccharides include glucosaminoglycan, hyaluronic acid, heparin, low molecular weight heparin, or ultra low molecular weight heparin, or derivatives thereof, or sulfated forms of the above-mentioned polysaccharides, for example, polysulfated forms, and And / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

  Antibodies are globular plasma proteins (about 150 kDa), also known as immunoglobulins, which share the basic structure. These are glycoproteins because they have a sugar chain attached to an amino acid residue. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (contains only one Ig unit), and the secretory antibody is also a dimer having two Ig units such as IgA, a teleost fish It can also be a tetramer with 4 Ig units like IgM, or a pentamer with 5 Ig units like IgM of a mammal.

  The Ig monomer is a "Y" shaped molecule comprised of four polypeptide chains, ie, two identical heavy chains and two identical light chains linked by disulfide bonds between cysteine residues It is. Each heavy chain is about 440 amino acids in length, and each light chain is about 220 amino acids in length. The heavy and light chains each contain intra-chain disulfide bonds that stabilize their folded structure. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (e.g., variable or V and constant or C) based on their size and function. These have the characteristic immunoglobulin folds that create a "sandwich" shape in which two beta sheets are held together by the interaction between conserved cysteine and other charged amino acids.

  There are five types of mammalian Ig heavy chains represented by α, δ, ε, γ and μ. The type of heavy chain present defines the isotype of the antibody, which are respectively found in IgA, IgD, IgE, IgG and IgM antibodies.

  The different heavy chains are different in size and composition, α and γ contain about 450 amino acids, δ contains about 500 amino acids, and μ and ε have about 550 amino acids. Each heavy chain has two regions, a constant region (CH) and a variable region (VH). In one species, the constant regions are essentially identical for all antibodies of the same isotype but differ for antibodies of different isotypes. Heavy chains γ, α, and δ have constant regions composed of three tandem Ig domains and a hinge region to add flexibility, and heavy chains μ and ε have four immunoglobulins Have a constant region composed of domains. The variable region of the heavy chain is different for antibodies produced by different B cells but the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids in length and is comprised of a single Ig domain.

  In mammals, there are two types of immunoglobulin light chains represented by λ and κ. The light chain has two consecutive domains, one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211-217 amino acids. Each antibody has two light chains that are always identical, and for each mammalian antibody there is only one type of light chain kappa or lambda.

  Although the general structure of all antibodies is very similar, the unique properties of a given antibody are determined by the variable (V) region, as detailed above. More specifically, three variable loops for each light chain (VL) and three heavy chains (HV) are involved in antigen binding, ie, its antigen specificity. These loops are called complementarity determining regions (CDRs). Because the CDRs from both the VH and VL domains contribute to the antigen binding site, it is the combination of heavy and light chains that determines ultimate antigen specificity, not either alone.

  An "antibody fragment" comprises at least one antigen binding fragment as defined above and exhibits essentially the same function and specificity as the whole antibody from which the fragment is derived. Limited protein digestion with papain cuts the Ig prototype into three fragments. Two identical amino terminal fragments, each comprising one complete light chain and about half a heavy chain, are antigen binding fragments (Fabs). The third fragment, which is identical in size but contains a carboxyl terminus at half of both heavy chains with interchain disulfide bonds, is a crystallizable fragment (Fc). Fc comprises a carbohydrate, a complementary binding site, and an FcR binding site. Limited pepsin digestion results in a single F (ab ') 2 fragment containing both the Fab fragment and the hinge region containing the H-H interchain disulfide bond. F (ab ') 2 is bivalent for antigen binding. The disulfide bond of F (ab ') 2 can be cleaved to obtain Fab'. In addition, heavy and light chain variable regions can also be condensed to form single chain variable fragments (scFv).

  Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts include, for example, HCl or HBr salts. The basic salt is, for example, an alkali or an alkali metal, for example, a cation selected from Na + or K + or Ca 2+, or an ammonium ion N + (R 1) (R 2) (R 3) (R 4) R4 independently of one another: hydrogen, optionally substituted C1 to C6 alkyl group, optionally substituted C2 to C6 alkenyl group, optionally substituted C6 to C10 aryl group, or optionally substituted C6 to C10 A salt having a heteroaryl group). Further examples of pharmaceutically acceptable salts are described in "Remington's Pharmaceutical Sciences" 17th edition, Alfonso R. et al. Gennaro (ed.), Mark Publishing Company, Easton, Pa. , U. S. A. , 1985 and Encyclopedia of Pharmaceutical Technology.

  Pharmaceutically acceptable solvates are, for example, hydrates.

  The button can include several components. The button can include two components. The button can include a plastic component and a metal component. The plastic component can comprise polyoxymethylene or other plastic material. The plastic component can be made by injection molding. The metal component can comprise, for example, aluminum. Alternatively, the metal component can comprise other metal materials. The outer surface of the metal component can be anodized. Anodizing provides a high quality wear resistant exterior surface to metal components. Furthermore, it enables the application of various metallic colors to the metallic component.

  The plastic component is at least partially received by the metal component. Thus, the plastic component can be the inner component of the button. The metal component can be an external or external component of the button. The metal component is configured to be manipulated by the user for dose setting and dosing. Specifically, the metal component is rotated by the user during dose setting. The metal component can in particular comprise an outer surface adapted to be gripped by the user. For example, the metal component can include at least one gripping feature.

  The outer metal component provides a high quality wear resistant outer surface of the button. Therefore, provision of a robust and long-lived device is promoted. In addition, the surface of the button is provided with various metallic colors. Thus, a drug delivery device with high quality aesthetics is provided. In addition, the light weight of the inner plastic component provides a very lightweight and cost effective device.

  According to one embodiment, the metal component comprises an aperture for receiving the plastic component. In other words, the metal component can include an open end. The other end opposite to the open end of the metal component is at least partially closed. Thus, the metal component can comprise a tubular body open on one side.

  The plastic component can include the largest outer diameter. The diameter of the aperture or open end of the metal component may be smaller than the largest outer diameter of the plastic component. The plastic component and the metal component are pushed relative to one another. In this way, the metal component and the plastic component are prevented from being separated by the user. Thus, a robust and compact button is provided. Therefore, the provision of a long-lived and robust device is promoted.

  According to one embodiment, the plastic component is elastically deformable at least in part. For example, when the plastic component is compressed during assembly of the button to allow the use of a bump-over design to achieve robust mechanical retention of the metal component, the plastic configuration At least a portion of the element elastically bends radially inward. In this way, assembly of the button is simplified. Furthermore, the resiliently flexible plastic component ensures a tight interface between the two components when the plastic component and the metal component are fixed to one another.

  According to one embodiment, the metal component is formed on the plastic component. The shapes of the plastic component and the metal component are at least partially applied to one another. Specifically, the outer surface of the metal component is at least partially applied to the outer surface of the plastic component.

  During assembly of the button, compression of the two components takes place. Thereby, the design of the plastic component allows the plastic component to be resiliently bent inwards, whereby a metal component is formed on the plastic component. In this way, a smooth surface of the button is achieved.

  According to one embodiment, the metal component is clamped to the plastic component. Specifically, the metal component is swaged to clamp the plastic component. The metal component is swaged into the plastic component. Thus, separation of the plastic component and the metal component is prevented after assembly to the button. In other words, the metal component and the plastic component are releasably coupled to one another. Therefore, provision of a safe and long-life device is promoted.

  According to one embodiment, the metal component and the plastic component are non-rotatably connected to one another. Thus, the rotation of the metal component during dose setting and / or dose delivery is transferred to the rotation of the plastic component.

  The plastic component can include at least one protrusion for non-rotatable coupling and / or alignment of the metal component and the plastic component. The plastic component can include a plurality of projections, for example three projections. The protrusions can project from the end face of the plastic component. The metal component can include at least one cutout. The metal component can include a plurality of cutouts, for example three cutouts. The cutouts are arranged at the end face of the metal component. Cutouts can be made by punching.

  The protrusions and cutouts are applied and arranged to mechanically cooperate with each other to non-rotatably connect and / or align the metal component and the plastic component. In particular, the projection is received by the cutout for the connection of the plastic component and the metal component. The movement of the metal component, and thus the movement of the plastic component, is transmitted to the drive mechanism of the device. Therefore, provision of an effective and reliable device is promoted.

  According to one embodiment, the plastic component comprises at least one gripping function. The gripping features can include one or more ribs and / or grooves. The gripping features are located on the outer surface of the plastic component. The metal component can include at least one mating gripping feature. The gripping features can include one or more ribs and / or grooves. The gripping features are located on the inner surface of the metal component. Preferably, the gripping function of the metal component is arranged on both the outer and the inner surface of the metal component. The gripping function of the metal component is stamped on the surface of the metal component. However, other ways of providing the metal component with a gripping function are also possible. The gripping function may, for example, be part of a deep drawing process of the metal component.

  The gripping features are applied and arranged to align the plastic component and the metal component when the plastic component is received by the metal component. Furthermore, the gripping function can provide a torque transfer between the plastic component and the metal component. In other words, the gripping function is provided to non-rotatably connect the plastic component and the metal component. The torque applied by the user is transmitted to the corresponding gripping function of the plastic component and thus the drive mechanism of the device via the gripping function of the metal component. In addition, the grip function of the metal component can be effective to make it easier for the user to grip the button. Therefore, provision of a user-friendly and effective device is promoted.

  According to one embodiment, the metal component is deep drawn. Metal components can be deep drawn from a metal sheet. After deep-drawing, the metal sheet can comprise an end face perpendicular to its longitudinal axis. Thus, a metal component is provided that includes the shape of an open tubular body on one side.

  According to one aspect, a method of assembling a button of a drug delivery device is provided. The button can be the button described above. The button can include a plastic component and a metal component. The plastic component and the metal component can correspond to the components described above. The method can include the following steps.

  A plastic component is at least partially inserted into the metal component. To this end, the metal component can include an aperture of a diameter large enough to receive at least a portion of the plastic component. The metal component can include an open end. The metal component can include a tip. The tip can be constructed of sections of gradually decreasing diameter which delimit the open end. The distance between the edges of the tip, ie the diameter of the apertures, may be large enough to at least partially insert the plastic component. The plastic component can include the largest outer diameter. The maximum outside diameter before the button is finally assembled can be less than the diameter of the aperture.

  In the next step, the metal component is swaged to clamp the plastic component to securely connect the metal component and the plastic component. A tool is provided for this purpose. The tool can include a conical shape. However, other shapes of tools are also possible. By means of the tool, the open end of the metal component is swaged with respect to the plastic component. By means of the tool, the open end of the metal component is compressed and deformed plastically.

  The plastic component can include a bump feature. Bump features are located on the outer surface of the plastic component. The bump features can extend circumferentially around the outer surface of the plastic component. The bump features may extend as a continuous feature or may be separated into discrete areas. The metal component, in particular its open end, is swaged over the bump function. The metal component is swaged on the bump function all around the plastic component. Thereby, the metal component, in particular its open end, can be deformed plastically. Thus, the metal component, in particular its open end, is formed on the plastic component.

  During swaging of the metal component into the plastic component, the plastic component, or at least a portion thereof, is elastically deformed radially inward, whereby the metal component is over-formed ). Once released, the plastic components will at least partially spring back, thereby creating a radial preload between the components and ensuring a tight interface between the plastic component and the metal component. Become. Thus, a sturdy button is provided that includes a smooth surface. Thus, the provision of a reliable and robust device is facilitated.

  According to one aspect, a drug delivery device is provided. The device can include a button. The button can include the button described above. The button can be assembled as described above. The device can be a reusable drug delivery device. In other words, the device can include a replaceable cartridge. However, in an alternative embodiment, the device can be a disposable device.

  The device can include a rotatable sleeve. The sleeve can be rotated during dose setting and dose delivery. The plastic component can include at least one ratchet feature. The plastic component can include multiple ratcheting features, for example two or more ratcheting features. A ratcheting feature is disposed on the inner surface of the plastic component.

  The ratcheting function is applied and arranged to mechanically cooperate with the sleeve, for example the corresponding ratcheting function of the sleeve, to provide audible feedback during dose delivery. Audible feedback can indicate to the user that the device is dosing the drug when the button is depressed after being dialed in the incremental direction. In this way, a device is provided that is very easy for the user to handle.

  According to one embodiment, the device can include a drive mechanism. The drive mechanism may be an internal member of a device adapted and arranged to communicate the movement of the button within the device to eject the drug. The drive mechanism can include, for example, the sleeve described above. The plastic component can include at least one snap feature. The plastic component can include multiple snap features, for example two, three or more snap features. The snap feature can project longitudinally from the plastic component. The snap feature is adapted and arranged to mechanically cooperate with the drive mechanism of the device or components of the drive mechanism to non-rotatably couple the button and the drive mechanism. In this way, a reliable and effective device is provided.

  It will be appreciated that the functions relating to the different aspects or embodiments described above and below can be combined with one another.

  Further features and improvements will be apparent from the following description of exemplary embodiments in conjunction with the accompanying drawings.

FIG. 1 is a schematic view of a drug delivery device with a cap attached according to the present invention. FIG. 2 is a schematic view of the drug delivery device of FIG. 1 uncapped and 79 units of dose dialed. Figure 2 is a schematic exploded view of the components of the drug delivery device of Figure 1; FIG. 2 is a schematic view of the outer housing of the drug delivery device of FIG. 1; FIG. 2 is a schematic view of the inner body of the drug delivery device of FIG. Figure 5b is a schematic view of a detail of the inner body of Figure 5a; FIG. 2 is a schematic view of a cartridge holder of the drug delivery device of FIG. FIG. 2 is a schematic view of a first display member component of the drug delivery device of FIG. 1; Fig. 7b is a schematic view of a detail of the first display member of Fig. 7a; FIG. 7 is a schematic view of a second display member component of the drug delivery device of FIG. 1; FIG. 2 is a schematic view of a first driver component of the drug delivery device of FIG. 1; FIG. 7 is a schematic view of a second driver component of the drug delivery device of FIG. 1; FIG. 7 is a schematic view of a third driver component of the drug delivery device of FIG. 1; FIG. 2 is a schematic view of a final dose nut of the drug delivery device of FIG. FIG. 2 is a schematic view of the clutch components of the drug delivery device of FIG. FIG. 2 is a schematic view of a first clicker component of the drug delivery device of FIG. 1; FIG. 2 is a schematic view of a second clicker component of the drug delivery device of FIG. FIG. 2 is a schematic view of the button of the drug delivery device of FIG. 1; FIG. 7 is a schematic cutaway view of the proximal portion of the drug delivery device of FIG. 1 in a zero unit position where the button is released. FIG. 2 is a schematic cut-away view of the proximal portion of the drug delivery device of FIG. 1 in a position where a unit is dialed. FIG. 7 is a schematic cutaway view of the proximal portion of the drug delivery device of FIG. 1 in a zero unit position where the button is pressed. Figure 2 is a schematic cut-away view of the drug delivery device proximal portion of Figure 1; FIG. 2 is a schematic internal perspective view of the proximal portion of the drug delivery device of FIG. 1; FIG. 21b is a schematic cut-away view of the proximal portion of the drug delivery device of FIG. 21a. Figure 2 is a schematic cut-away view of the dose button of the device of Figure 1 prior to final assembly. Figure 2 is a schematic cut-away view of the dose button of the device of Figure 1 after final assembly. Figure 23 is a schematic view of the method steps of assembling the button of Figure 22a; Figure 22b is a schematic view of a portion of the dose button of Figure 22b in an assembled state; FIG. 22b is a schematic view of the components of the dose button of FIG. 22a prior to assembly. FIG. 22b is a schematic view of the components of the dose button of FIG. 22a prior to assembly. FIG. 22b is a schematic cut-away view of the assembled dose button of FIG. 22b.

  1 and 2 show a drug delivery device 1 in the form of an injection pen. The device 1 has a distal end (lower end in FIG. 1) and a proximal end (upper end in FIG. 1). The term "distal end" can refer to the end of the device or component thereof that is located closest to or closest to the dispensing end of the device. The term "proximal end" can refer to the end of the device or component thereof that is located furthest or farthest from the dispensing end of the device 1.

  The components of the drug delivery device 1 are shown in more detail in FIG. The drug delivery device 1 includes an outer housing member 10, an inner body 20, a piston rod 30, a driver 40, a nut 50, a display member 60, a button 70, a cartridge holder 80 for receiving a cartridge 81, a clutch 90, a clicker 100, a spring. 110, a cap 120, and a window insert 230. A needle device (not shown), including a needle hub and a needle cover, is provided as an additional replaceable component. The piston rod 30 includes a bearing 31. The driver 40 includes a distal driver member 41, a proximal driver member 42, and a coupler 43. The display member 60 includes a number sleeve 61 and a dial sleeve 62. Clicker 100 includes a distal clicker member 101, a proximal clicker member 102, and a spring 103.

  The outer housing member 10, also shown in FIG. 4, is a generally tubular element having a distal member 11 and a proximal member for attaching the inner body 20, and a maximum unit (e.g. 80 U) stop is engaged A rotary hard stop 12 is provided on its inner surface (not shown) which contacts the mating surface of the display member 60 when it is actuated. The end face also functions as a dose dispensing stop for the button 70, the hole in the end face centering the display member 60 both during dial setting and during dosing. An aperture 13 is provided to receive the window insert 230. The outer body 10 provides the user with a surface to grip and counteract during dosing.

  The inner body 20 is a generally tubular element having different diameter areas. As seen in FIGS. 17-19, the inner body 20 is received by the outer body 10 and permanently fixed thereto to prevent any relative movement of the inner body 20 relative to the outer body 10. The inner body functions to guide the clicker and final dose nut 50 by means of internal splines to accommodate the drive mechanism therein, to provide an internal thread for driving the piston rod 30 (lead screw), a number sleeve 61 and It has the function of supporting and guiding the dial sleeve 62 by the outer thread form, the function of fixing the cartridge holder 80, and the function of fixing the outer body 10 and the window insert 230.

  The outermost diameter of the inner body 20 also forms part of the visual design and remains visible when the cap 120 is fixed to the cartridge holder 80 as a ring separating the cap 120 from the outer body 10 . The visible ring also has a recess that aligns with the cap snap feature on the cartridge holder 80 to indicate that the cartridge holder has been properly fitted.

  An outer thread 21 is provided on the outer surface of the inner body 20. Further, splines 22 (FIG. 5 b) are provided on the inner surface of the inner body 20. These internal splines 22 guide the clicker 100 axially during dial setting and during dosing, and also prevent the final dose nut 50 from rotating. Some of the splines 22 are wider to ensure proper rotational assembly of the internal components, and these wider splines are on the distal drive sleeve 41 while the final dose nut 50 is assembled. It may have an inlet with a step and a beveled surface to facilitate hitting against the stop surface and rotating. At the open end shown in FIG. 5 b there is an additional short spline, which is used together with the alternate long splines 22 to lock the button 70 (dose dial grip) non-rotatably at the end of the dosing and Serves to increase the strength of the 0U dial stop when the key is depressed. This is achieved by engagement with the male spline feature on the clutch component 90.

  The bayonet function 23 guides the cartridge holder 80 into the mechanism during cartridge replacement to compress the cartridge biasing spring 110 and then shortens the cartridge holder 80 to reduce axial play within the mechanism. Retract the distance. The internal snap feature of the inner body 20 locks the cartridge holder 80 non-rotatably when it is properly fitted. These snap characteristics aim to prevent the user from fitting the cartridge holder 80 incompletely, and the cartridge biasing spring 110 ejects the cartridge holder 80 when the snaps are not at least beginning to engage. . The window retaining nose 24 retains the window insert 230 when the outer body 10 and window insert 230 assembly is axially inserted into the inner body 20. Two diametrically opposed stop faces 25 define the rotational end position of the number sleeve 61. This end position is the end of the minimum dose (0 U) dose detent position.

  The piston rod 30 is an elongated element with two mutually overlapping outer threads 32, 33 in opposite directions. One of these threads 32 engages the inner thread of the inner body 20. A disc-like bearing 31 is provided at the distal end of the piston rod 30. The bearing 31 may be a separate member as shown in FIG. 3 or may be attached to the piston rod 30 as an integral component via a predetermined breaking point.

  The piston rod 30 transmits the dosing load from the driver 40 to the bearing 31 so that the torque generated by the threaded interface of the driver 40 against the piston rod 30, the piston rod is a screw in the inner body 20. Converting to additional axial loading as it passes through the mountains produces a mechanical benefit greater than 1: 1. The piston rod 30 is reset by pushing on the bearing 31, which in turn causes the piston rod to rotate back into the inner body 20. This disengages the distal drive sleeve 41 and then rotates to reset the final dose nut 50 back to its starting position on the distal drive sleeve 41.

  The driver 40 is a generally tubular element having three components in the embodiment shown in the drawings, which are depicted in more detail in FIGS. 9-11.

  The distal drive sleeve 41 engages the piston rod thread 33 to drive the piston rod 30 in the inner body 20 during dose delivery. The distal drive sleeve 41 is also permanently connected to the coupler 43, which is releasably engaged with the proximal drive sleeve 42 by means of a reset clutch function. The two halves of the drive sleeve 41 are non-rotatably axially connected during dial setting and dosing, but are rotationally decoupled so that they can rotate relative to one another during device reset.

  Outer thread 44 engages final dose nut 50. This thread form has a shallow first step (left side in FIG. 9) on which the nut 50 moves to count most of the dial setting unit, the final dose nut before engaging the stop surface Three steps, a quick step with fast axial movement and the last shallow section ensuring that the axial constraint on the nut 50 extends over a suitable length of thread form when the stop surface is engaged Have. Four equally spaced stop surfaces 45 engage the mating stop surfaces 51 on the final dose nut 50 to limit the number of units that can be dialed. A spline 46 is provided at the proximal end of the distal drive sleeve 41 to transmit torque between the coupler 43 which snaps onto the distal drive sleeve 41.

  The proximal drive sleeve 42 shown in FIG. 10 supports the clicker component 100 and the clutch 90 and transmits rotational movement from the dose button 70 to the coupler 43 and the distal drive sleeve 41.

  A tooth feature 47 located at the distal end of the proximal drive sleeve 42 engages a reset clutch feature on the coupler 43 to couple the drive sleeve halves during dial setting and dosing. During reset, these teeth 47 disengage.

  Several splines are provided on the outer surface of the proximal drive sleeve 42 that engage the distal and proximal clicker members 101, 102 to prevent relative rotation during dial setting and dosing. Another spline located in the middle region of the proximal drive sleeve 42 engages the clutch 90 components. These splines are non-rotationally symmetrical so that the various clicker components can not be incorrectly assembled upside down.

  The proximal portion of the proximal drive sleeve 42 has four arms or fingers 48, as seen in FIG. The hook-like bearing surface 49 lies below the flange segment at the end of the flexible finger 48 (as viewed in FIG. 10). The flexible fingers 48 are separated by gaps or slots, which provide space for the button 70 to snap into the clutch 90 and further, during assembly of the proximal drive sleeve 42 to the dial sleeve 62. Enable to turn inwards. After assembly, the hook 49 receives the reaction from the spring 103 to hold the proximal drive sleeve 42 against the dial sleeve 62. During dosing, the button 70 depresses the spring 103 via the clutch 90 and the clicker component, this spring 103 reacts against the proximal drive sleeve 42 through the coupler 43 and then this proximal drive sleeve Axial loads are applied to the dial sleeve 62 through these bearing surfaces. This axial load drives the dial sleeve 62 and thus drives the number sleeve 61 along the helical thread of the inner body 20 until the 0U stop face of the number sleeve 61 contacts the inner body 20 1 Put back into the body of the.

  The coupler 43 shown in FIG. 11 non-rotatably couples the two halves of the drive sleeve 42 together during dial setting and dosing while allowing decoupling during reset. The coupler 43 must also transmit the final dose protection stop load from the proximal drive sleeve 42 to the distal drive sleeve 41. Two sets of teeth are provided in the coupler 43 which engage the teeth 46 and 47 respectively. The coupler 43 is snapped onto the distal drive sleeve 41 to allow limited relative axial movement with respect to the proximal drive sleeve 42.

  A nut 50 is provided between the inner body 20 and the distal drive sleeve 41 of the drive 40. Stop surface 51 is located on the proximal surface of final dose nut 50 to limit the number of units that can be dialed when stop surface 51 contacts stop surface 45 of distal drive sleeve 41. The function of the final dose nut 50 is to prevent the user from dialing out beyond a limited amount. This limitation is based on the doseable volume of the cartridge 81, and when reached the user has to replace the cartridge 81 and reset the device.

  The outer rib 52 of the nut 50 engages the spline 22 of the inner body 20. The inner thread 53 of the nut engages the outer thread 44 of the distal drive sleeve 41. As an alternative embodiment, splines and ribs may be provided at the interface between the nut 50 and the driver 40 and threads may be provided at the interface between the nut 50 and the inner body 20. As another alternative, the nut 50 is designed, for example, as a half nut.

  The display member 60 is a generally tubular element comprised of a numeric sleeve 61 and a dial sleeve 62, which are configured to axially constrain and non-rotatably constrain these two components Snap together during assembly, thus acting as a single piece.

  The main function of the number sleeve 61 depicted in FIG. 8 is to provide a surface on which the dose number can be printed to indicate the dialed dose, the piston rod when the inner body 20 is threaded Guide the helical path of the internal mechanism during dial setting to follow the helical thread shape on 30 and attach it to the dial sleeve 62.

  The number sleeve 61 is designed to be completely sealed in the outer body 10 during dial setting and dosing, so that only the dial setting dose is visible to the user through the window aperture. The numeric sleeve has a 0U (minimum dose) stop surface 63 to limit its travel when dialed inwards, but an 80U (maximum dose) stop surface on the dial sleeve 62, which limits the dial set outer condition Located in At the end of each dosing stroke, this stop surface 63 engages the mating surface 25 on the inner body 20 to limit the rotational position of the number sleeve 61.

  The helical drive surface 64 forms a thread which guides the number sleeve 61 to follow the helical path 21 on the inner body during dial setting and dosing.

  The dial sleeve 62 is assembled to the number sleeve 61 so that relative movement is not possible after assembly. The member is made as a separate component to enable both molding and assembly. Also, the number sleeve 61 is preferably white, for example to obtain contrast to the black dose number, while the color of the dial sleeve 62 is adapted to be aesthetically pleasing or to distinguish the drug type Can be selected.

  At the dose proximal end, the dial sleeve 62 has an inner clutch feature 65 which engages the clutch 90 during dial setting and disengages the clutch 90 during dosing. These clutch features 65 lock the dial sleeve 62 non-rotatably to the clutch 90 during dial setting and when the 0U and 80U stops are engaged. When the button 70 is depressed, these clutch features disengage and allow the dial sleeve 62 and number sleeve 61 to rotate back to the 0 U start position while the clutch 90 and drive mechanism move axially. Make it

  The dial sleeve 62 is rotated outward by engagement with the clutch 90 and the number sleeve 61 during dial setting and is applied by the proximal drive sleeve 42 to the flange like bearing surface 66 at the end of the dial sleeve during dosing. Receives an axial force and reverses inward. The bearing surface 66 engages the flexible arm 48 of the proximal drive sleeve 42 during dosing. The two diametrically opposed surfaces 67 engage the outer body 10 when the maximum dose (e.g. 80 U) is dialed to form a maximum dose stop surface.

  The dial sleeve 62 includes a clicker or ratchet arm 68 (FIGS. 7a, 7b, 21a and 21b). A ratchet arm 68 projects radially outwardly from the distal sleeve 62. The ratchet arm 68 engages with the ratchet feature 132 on the button 70 (dose dial grip) to provide audible feedback during dosing, providing a click sound for each unit delivered. This further prevents the user from gripping the number sleeve 61 with the button 70 depressed and rotating it out of the partially dialed position. This will cause the piston rod 30 to reverse, which will result in an underdose for subsequent dial setting doses. This can further strengthen the 0U fastener.

  The button 70 shown in FIG. 16 and in more detail in FIGS. 20-26 functions as a dose dial grip. The button 70 includes two components. The two components are coupled to one another such that relative rotation and axial movement between the two components is prevented. In this embodiment, the two components are nonreleasably coupled to one another. In other words, the two components can not be separated without destroying the button 70. In one alternative embodiment, the two components can be releasably coupled to one another.

  As seen, for example, in FIGS. 20, 21b, 22a and 22b, the button 70 includes an inner or plastic component. Plastic component 130 includes a plastic liner. The plastic component 130 is, for example, injection molded. Plastic component 130 includes a central portion 130a (FIGS. 22a and 22b). The central portion 130 a projects distally from the plastic component 130 when the button 70 is assembled to the device 1. Plastic component 130 includes a proximal portion 130b. The shape of the proximal portion 130b is similar to a button. The proximal portion 130b has a larger outer diameter than the central portion 130a. The central portion 130a and the proximal portion 130b are integrally formed.

  The button 70 further includes an outer component or metal component 131 (FIGS. 20, 21b, 22a and 22b). The metal component 131 comprises a metal shell. Metal component 131 includes, for example, aluminum. Alternatively, metal component 131 can also include other metal materials. The metal component 131 is deep drawn.

  The metal component 131 is in the form of a tube. The metal component 131 comprises a hollow body. The metal component 131 is open on one side. Specifically, metal component 131 includes an aperture 131a or an open end. The aperture 131 a is located at the distal portion of the metal component 131. The proximal portion of the metal component 131 is at least partially closed. A metal component 131 is disposed around the plastic component 130, as described in detail below. A metal component 131 is disposed on the outer surface of the button 70 operated by the user during operation of the device 1.

  Metal component 131 and plastic component 130 are non-rotatably axially connected to one another. For this purpose, the plastic component 130 comprises at least one protrusion 139 (FIG. 25b). In this embodiment, the plastic component 130 includes three protrusions 139. Protrusions 139 can include, for example, logo features designed to identify device 1 and / or the manufacturer of device 1. The protrusions 139 can, for example, be made the same shape. Alternatively, the protrusions 139 can include different shapes. For example, one protrusion 139 may be longer than the other protrusion 139. The protrusions 139 can also include the shape of a circular segment. The protrusions 139 can also be arranged like circular segments. Protrusions 139 project proximally from plastic component 130. Protrusions 139 are disposed on the proximal end surface of plastic component 130. The protrusion 139 is disposed on the proximal end surface of the proximal portion 130b.

  The metal component 131 comprises at least one cutout 138 (FIG. 25a). In this embodiment, the metal component 131 comprises three cutouts 138. Cutout 138 is disposed in the proximal portion of metal component 131. Cutout 138 is disposed on the proximal end or top surface of metal component 131. The cutouts 138 are punched into the metal component 131. The cutouts 138 are adapted and arranged to mechanically cooperate with the projections 139 of the plastic component 130. When the button 70 is assembled, the projections 139 are received by the cutouts 138, whereby the plastic component 130 and the metal component 131 are non-rotatably aligned (FIG. 22b).

  The plastic component 130 further includes a gripping feature 137b (FIGS. 25b and 26). The metal component 131 includes a mating gripping feature 137a. The gripping features 137 b of the plastic component 130 include a plurality of grooves disposed along the outer surface of the plastic component 130. In this embodiment, the gripping features 137b include nine grooves. However, there may also be embodiments where there are more than nine, for example ten or twelve grooves, or less than nine, for example five grooves. The groove is in particular arranged along the side of the proximal portion 130b (FIG. 22b). The grooves are adapted and configured to receive the corresponding gripping features 137a of the metal component 131 (FIGS. 25a and 26).

  The gripping function 137a of the metal component 131 comprises a plurality of grooves and ribs arranged along the side of the metal component 131. Specifically, the outer surface of the metal component 131 is, for example, such that grooves are created on the side of the metal component 131 and corresponding ribs are created on the inner side of the metal component 131 as seen in FIG. Compressed or formed. In other words, the outer and inner sides of the metal component 131 can include wavelike structures.

  When the button 70 is assembled, the gripping features 137a, 137b mechanically cooperate with one another to align the plastic component 130 and the metal component 131. Specifically, when the button 70 is assembled, the ribs on the inner side of the metal component 131 are guided in the grooves on the outer side of the plastic component 130. Furthermore, the plastic component 130 and the metal component 131 are non-rotatably connected by mechanical cooperation of the gripping functions 137a, 137b. The gripping function 137a further enables the user to easily grip the outer surface of the button 70 in order to rotate the button 70 during operation of the device 1.

  The metal component 131 and the plastic component 130 are preferably nonreleasably connected to one another. The metal component 131 and the plastic component are clamped to one another.

  The aperture 131a or open end described above has a diameter. The open end has a circumferentially extending tip 140 which delimits the aperture 131a (FIGS. 22a, 22b and 24). The diameter of the aperture 131a prior to assembly of the button 70 is a diameter large enough to receive the plastic component 130, specifically the proximal portion 130b of the plastic component 130 (see FIG. 22a). In other words, the diameter of the aperture 131a prior to assembly of the button 70 is greater than the largest diameter of the proximal portion 130b of the plastic component 130. The diameter of the aperture 131a after the button 70 is finally assembled, ie after the plastic component 130 and the metal component 131 are nonreleasably connected to each other, is greater than the maximum outside diameter of the proximal portion 130b of the plastic component 130. Too small.

  In the following, the method of assembling the button 70 will be described in detail in conjunction with FIGS. 22a, 22b, 23 and 24.

  First, a plastic component 130 is provided. Furthermore, a metal plate is provided. In the next step, the metal plate is deep drawn. After deep-drawing, the metal sheet comprises an end face perpendicular to its longitudinal axis. This end face delimits the aperture 131a described above.

  The metal plate is then formed in a tubular shape to provide an aperture 131a or open end at the distal end. In this assembly process, the size of the apertures 131a is large enough to receive the plastic component 130 during the assembly process. In a further step, gripping features 137a and cutouts 138 are provided by stamping and / or punching. Thereafter, the deep drawn metal plate is anodized.

  Next, the plastic component 130, specifically the proximal portion 130b, is inserted into the aperture 131a of the metal component 131. The plastic component 130 can engage the cutout 138 and the projection 139 when the plastic component 130 reaches its final position relative to the metal component 131, whereby the metal component 131 and the plastic component 130 Are inserted so that they are aligned.

  Furthermore, when the plastic component 130 is inserted, the gripping features 137a, 137b engage one another, thereby aligning the plastic component 130 and the metal component 131. In addition, the gripping features 137a, 137b aid in the non-rotatable connection of the metal component 131 and the plastic component 130 during use of the device.

  The plastic component 130 is moved in a proximal direction relative to the metal component 131 and the gripping functions 137a, 137b guide its movement. When the plastic component 130 reaches its final position with respect to the metal component 131, the proximal end surface of the plastic component 130 mechanically cooperates with the inner surface of the proximal end surface of the metal component 131, whereby the plastic configuration The gate point 136 (FIG. 25b) located at the proximal end of the element 130 is hidden. When the plastic component 130 reaches its final position with respect to the metal component 131, the cutout 138 mechanically cooperates with the projection 139, whereby the complete rotational alignment of the plastic component 130 and the metal component 131 is achieved. Will be assured. These protrusions 139 and cutouts 138 again serve to transfer torque between the two components 130, 131 during use of the device.

  Once the plastic component 130 has reached its final position, the plastic component 130 and the metal component 131 are secured to one another, preferably non-releasably. Specifically, plastic component 130 and metal component 131 are clamped together. For this purpose, a swaging tool 134 is provided (FIG. 23). The swaging tool 134 may be conical. The swage tool 134 causes the distal open end to be pressurized such that the tip 140 is formed inwardly (Figure 22b).

  The swaging tool 134 exerts a force on the distal end of the metal component 131. The force is at least partially directed radially inward. Thereby, the plastic component 130 is elastically deformed radially inward by contacting the metal component 131 or by directly contacting the swaging tool. The plastic component 130 includes a bump function 133. The bump features 133 are circumferentially disposed around the outer surface of the plastic component 130, specifically the proximal portion 130b. During final assembly of the button 70, the distal end of the metal component 131 is swaged over the bump feature 133 around the entire circumference and thereby clamped in place. Thereby, the tip 140 is plastically deformed radially inward to create a smooth surface of the button 70.

  Plastic component 130 includes an engagement feature 135. The engagement feature 135 can be a lip. The engagement feature 135 is disposed on the outer surface of the plastic component, specifically its proximal portion 130b. The engagement features 135 extend circumferentially around the proximal portion 130b. When the proximal portion 130b is fully inserted into the metal component 131, the engagement feature 135 is in place and comes into mechanical cooperation with the distal end of the metal component 131 (FIG. 22a). When the distal end of the metal component 131 is plastically deformed during final assembly, the tip 140 is formed inwards, thus, as seen in FIGS. 22 b and 24, the engagement feature 135 and the machine Will cooperate with each other. The engagement feature 135 prevents access to the tip 140 so that the user can not lift the edge of the metal component 131 from the bottom to remove the metal component 131 from the plastic component 130.

  When no further force is exerted on the metal component 131, the plastic component 130 is at least partially bent radially outwards back, whereby the tightness between the plastic component 130 and the metal component 131 is achieved. Interface is ensured. The smooth anodized finish and negative taper of metal component 131 make it impossible to obtain the traction needed to manually remove metal component 131 from plastic component 130 without the use of tools. It will be very difficult if not. The button 70 is then ready to be assembled to the further components of the device 1.

  The assembled button 70 is held by the clutch 90 to transfer the user's action to the clutch 90. For this purpose, the plastic component 130, in particular the central part 130a, comprises four arms 73 projecting in the distal direction. The arms 73 include hook-like snap features 74 at their respective distal ends. Arm 73 forms a splined surface that engages clutch 90 to transmit torque from button 70 to distal sleeve 62 and proximal drive sleeve 42 via clutch 90.

  The arm 73 is inserted into the clutch 90 due to the mechanical connection between the clutch 90 and the button 70. When the arm 73 is inserted, the snap feature 74 engages the aperture or snap feature 93 in the clutch 90. The snap feature 74 is designed with an angled undercut surface to maintain engagement when an axial load is applied to pull the button 70 out of the pen body 10. The space between the arms 73 is such that the flexible arm 48 of the proximal drive sleeve 42 engages the button 70 and the clutch 90 when the button 70, specifically the metal component 131, is depressed and released during dose dosing. Define a pocket that provides clearance for free sliding.

  The plastic component 130 further includes the ratchet feature 132 described above. A ratcheting feature 132 is disposed on the inner surface of the plastic component 130 (see FIGS. 16 and 21b). The ratcheting function 132 comprises a plurality of ratcheting teeth 71. The ratchet teeth 71 engage the ratchet arm 68 (FIGS. 7a and 7b) of the distal sleeve 62 and act as a dosage clicker to provide audible feedback (ratchet click). The plastic component 130 further includes an end face 72 which acts as a dose complete stop with the outer body 10 (FIG. 16). Thus, the end face 72 acts to define an end position as it contacts the outer body 10 during dosing, so as to provide a very positive stop which improves dose accuracy.

  The cartridge holder 80 is attached to the inner body 20 by a bayonet connection 82 and contains a glass ampoule or cartridge 81 containing the medication to be dispensed. The cartridge holder 80 includes an aperture 83 on the rear surface (as viewed in FIG. 6) which prevents the ampoule from falling out when the cartridge holder is removed from the inner body 20 when gripped by the user . A dose scale is printed on the front. The threaded distal end 84 is used to attach a disposable pen needle.

  The tubular clutch 90 is provided between the display member 60 and the button 70. The clutch 90 is fixed relative to the button 70 and holds the button as described above, and together they pivot relative to the proximal drive sleeve 42 when the button 70 is depressed during dosing. Move in the direction to disengage the clutch teeth from the dial sleeve 62. It also transmits torque from the button 70 to the proximal drive sleeve 42 and transmits dial setting load and 0U / 80U stop load from the button through the clutch teeth to the dial sleeve and the numeric sleeve.

  Drive sleeve splines 91 provided on the inner surface of the clutch 90 engage the proximal drive sleeve 42. The distal end face is provided with a clutch biasing tooth 92 which mates with a similar tooth on the proximal clicker member 102 to bias the clutch spring 103 in the button outer position (dial set dose). Acting to ensure that it is non-rotatably locked to the proximal clicker member 102. The teeth 92 are shallow in height such that the proximal clicker member 102 does not engage the splines on the proximal drive sleeve 42 during dial setting. The four snap apertures or snap features 93 serve to hold the snap features 74 of the plastic component 130 of the button 70, as described above. The clutch has a spline 94 near its proximal end which locks onto the inner body 20 with the button 70 depressed at the end of dosing, allowing the user to rotate the button 70 below the 0 U position To prevent

  The clutch teeth 95 engage the clutch teeth 65 of the dial sleeve to non-rotatably connect the button 70 to the numeric sleeve 61 via the clutch 90. During dosing, the clutch moves axially to disengage these clutch teeth 95, whereby the dial sleeve 62 is released to rotate back into the device, while the clutch 90, and thus the driver 40. Move axially to dispense a dose.

  Clicker 100 includes a distal clicker member 101, a proximal clicker member 102, and a spring 103. The clutch spring 103 acts to bias the button 70 outward so that at the end of the dose the button 70 pops out to re-engage the clutch 90 with the dial sleeve 62 ready for dial setting. In addition, the clutch spring provides a spring force for the clicker component to function as a clicker and as a detent position for the number sleeve 61. In addition, the clutch spring allows the two halves 41, 42 of the drive sleeve to be disengaged during device reset, but remains in rotational engagement during dial setting and dosing.

  The distal clicker member 101 is permanently splined to the proximal drive sleeve 42 and engages the proximal clicker member 102 so that the proximal clicker member is splined to the inner body 20. During dial setting, as the drive sleeve rotates relative to the inner body, the two clicker members 101, 102 rotate with one another under the compressive force of the clutch spring 103. This force, combined with the clicker teeth formed on the end face of each clicker, results in a clicking sound and also results in a dial set detent position.

  During dosing, the two clickers 101, 102 are urged together under a dosing load, thus preventing relative rotation between the proximal drive sleeve 42 and the inner body 20 to deliver the dose. Drive the piston rod forward. The inner hole splines 104 always non-rotatably connect the distal clicker member 101 to the proximal drive sleeve 42, but when the button 70 is depressed during dosing and when the two clickers rest against each other during dial setting Allow free axial movement. The contours of both clicker teeth 105, 106 on the distal clicker member 101 and on the proximal clicker member 102 are identical and bear against each other under compressive loading from the spring 103 during dial setting.

  The proximal clicker member 102 is permanently splined to the inner body 20 by the outer splines 107 that prevent relative rotation with the inner body during dial setting and during dosing to provide a clicking sound during dial setting and during dosing Lock the proximal drive sleeve 42 non-rotatably. An additional cylindrically shaped spline 108 also non-rotatably connects the proximal clicker member 102 to the proximal drive sleeve 42 when the button 70 is depressed, which allows the user to hold 80 units with the button depressed. To prevent dialing over. The proximal clicker member 102 has, in addition to the main clicker teeth 106, clutch biasing teeth 109 on the opposite end face. These teeth mate with similar teeth 92 on the clutch so that, at the button outside position (dial set dose), the clutch is rotationally locked to the proximal clicker member 102 under the bias of the clutch spring 103 Make sure to be done.

  The cartridge biasing spring 110 is assembled as one of two components, the first on the lower side and the second on the upper side. This spring combination serves to apply an end load to the cartridge 81 at a tolerable extreme value, biasing the cartridge forward and against the end face of the cartridge holder 80 ferrule. This ensures that the friction between the needle cannula and the septum of the cartridge does not move the cartridge 81 axially relative to the cartridge holder 80 when the user removes and installs the needle. The biasing spring 110 also acts to provide a force against which the user must connect the cartridge holder 80, which can add tactile feedback of this bayonet joint. The spring 110 also serves to eject the cartridge holder 80 when the cartridge holder is not turned into a secure position, making this mistake noticeable to the user.

  The cap 120 serves to protect the cartridge holder 80 from damage and to protect the cartridge 81 itself from dust contamination into the area around the septum. The cap is designed to accommodate a standard pen syringe needle.

  The window insert 230 can include a lens that expands the dose number, for example, about 25% from its print size. The window insert 230 is back printed to protect the printed surface from wear and to maximize the light coming from the window aperture to provide uniform illumination of the dose numbers and the white areas around these numbers. . An arrow indicating the dialed dose is printed adjacent to the window aperture.

  In the following, the function of the drug delivery device and its components will be described in more detail with reference to FIGS. 17-19.

  The user must select a dose to use this device. In the start (rest) state shown in FIG. 17, the display member 60 indicates to the user the number of dialed doses. The number of units dialed can be viewed through the dose window 230 of the outer body 10. The threaded engagement between the display member 60 and the inner body 20 causes the display member 60 to spiral out of the device as the button 70 is rotated clockwise, gradually counting into the number of units to be delivered. FIG. 18 shows an intermediate stage of dial setting (e.g. 7 of 80 units).

  During dose setting, the button 70, the driver 40 and the display member 60 are non-rotatably locked together via the clutch 90. Furthermore, the button 70, the driver 40 and the display member 60 are axially connected. Thus, these three components spiral out of the outer housing 10 during dose setting. The clockwise rotation of the button 70 causes the driver 40 to rotate, and while doing so, the driver travels along the piston rod 30 which remains fixed during dial setting. The clicker arrangement 100 provides the user with tactile and audible feedback when setting up the dose. At a maximum settable dose of 80 units, the stop features 12 and 67 engage to prevent further dial settings.

  The final dose nut 50 provides the function of counting the number of dosage units. The nut 50 locks the device 1 at the end of the cartridge life, so that the user can not dial up any further drug. The final dose nut 50 and the driver 40 are connected via the threaded interface described above. Furthermore, the final dose nut 50 is assembled to the spline 22 such that the nut 50 and the inner body 20 are locked together (always) in a non-rotatable manner. As the driver 40 rotates during dial setting, the nut 50 will advance along the thread 44. The nut 50 always slides axially freely in the inner body 20 so that it can be advanced. The change in the pitch of the threads 44 shown in FIG. 9 towards the final dose axially accelerates the advancement of the nut 50 towards the end of the cartridge life lockout condition. At the end of life, the stop function 51 of the final dose nut 50 contacts the corresponding function 45 on the driver 40. The spline contact with the inner body 20 corresponds to any torque transmitted by these stop features 45.

  Once the desired dose has been dialed, device 1 is ready for dose dosing. Dose dosing basically requires pressing the button 70, and in particular the metal component 131, which causes the clutch 90 to disengage from the dial sleeve 62, thereby causing the display member 60 to Relative rotation with the button 70 is possible. In all conditions, the driver 40 and the button 70 are together locked non-rotatably by the engagement of the arm 73 and the finger 48 and by the spline 91 engaging the corresponding spline on the proximal drive sleeve 42 There is. That is, when the clutch 90 is disengaged (the button 70 is pushed), the button 70 and the driver 40 are locked together so as not to rotate, and the button 70, the driver 40 and the display member 60 are still in the axial direction Is linked to

  When dispensing a dose, the dose button 70 and the clutch 90 move axially relative to the mechanism that compresses the clutch spring 103. Since the proximal clicker member 102 is splined to the inner body 20 and the axial load through the clicker teeth 105, 106 locks the distal clicker member 101 non-rotatably to the proximal clicker member 102, this mechanism Although forced to move in a direction, the dial sleeve 62 and the numeric sleeve 61 rotate freely back into the outer housing 10. The interaction of the mating threads between the piston rod 30, the driver 40 and the inner body 20 provides a 2: 1 mechanical advantage. In other words, advancing the driver 40 axially causes the piston rod 30 to rotate, and this rotation advances the piston rod due to the threaded engagement of the piston rod 30 with the inner body 20. During dose dosing, the dosing clickers 68, 71 are active, which requires the button 70 and the display member 60. Medication clickers primarily provide the user with audible feedback that the drug is being dispensed.

  The end of this step is shown in FIG. At this point, the dose is complete, and when the user removes force from the end of the dose button 70, the clutch spring 103 pushes the dose button 70 back, causing teeth 65 and 95 between the clutch and the dial sleeve. Re-engage.

  Resetting the device begins with removing the cartridge holder 80 and replacing the empty cartridge with a full cartridge 81. When the cartridge holder is remounted, the plug of the new cartridge contacts the bearing 31, thereby pushing the piston rod 30 back into the housing. Initially, the piston rod 30 screws into the inner body 20 thereby axially disengaging the coupler 43 from the proximal drive sleeve 42 against the bias of the spring 103 . When disengaged, the coupler 43 begins to rotate freely with the distal drive sleeve 41 and continues so moving until the cartridge holder 80 axially engages the inner body 20. That is, the distal drive sleeve 41 is attached to the proximal drive sleeve 42, which is still non-rotatably constrained within the inner body 20 as the clicker members 101 and 102 are pushed by the spring 103 to be compressed together. Rotate against. As the distal drive sleeve 41 rotates, the final dose nut 50 is reset to its (distal) start position. Coupling the cartridge holder 80 to the inner body 20 retracts the mechanism by means of the bayonet structure 23 which allows re-engagement of the proximal drive sleeve 42 and the coupler 43 and thus the distal drive sleeve 41.

  The scope of protection is not limited to the examples given hereinabove. The present invention is embodied as respective novel features and combinations of features, and in particular all combinations of any of the features described in the claims, this feature or claim of this combination of features being claimed Included even if not explicitly stated in the scope or examples. The configurations of the embodiments described above can be combined. The layout, functionality and number of components can be varied in other embodiments.

DESCRIPTION OF SYMBOLS 1 drug delivery device 10 outer housing member 11 distal member 12 stop 13 aperture 20 inner main body 21 outer thread 22 spline 23 bayonet function 24 holding means 25 stop 30 piston rod 31 bearing 32 thread 33 thread 40 driver DESCRIPTION OF SYMBOLS 41 distal part 42 proximal part 43 coupler 44 thread 45 stop face 46 spline 47 tooth function 48 finger surface 49 bearing surface 50 stop nut 52 stop face 52 outer rib 53 inner thread 60 display member 61 numeral sleeve 62 dial sleeve 63 Stop face 64 Thread 65 Tooth 66 Contact function 67 Opposite face 68 Clicker 70 Button 71 Ratchet tooth / Clicker 72 End face 73 Arm 74 Snap function 80 Cartridge holder 81 Cartridge 82 Bayonet connection Part 83 Aperture 84 Distal end 90 Clutch 91 Drive sleeve spline 92 Clutch urging tooth 93 Snap function 94 Spline 95 Clutch tooth 100 Clicker 101 Distal clicker member 102 Proximal clicker member 103 Spring 104 Spline 105, 106 Clicker tooth 107 Outer spline DESCRIPTION OF SYMBOLS 108 forming spline 109 clutch urging tooth 110 spring 120 cap 121 distal end 122 proximal end 230 window 130 plastic component 130 a central portion 130 b outer or proximal portion 131 metal component 131 a aperture 132 ratchet function 133 bump function 134 swage tool 135 engaging function 136 gate point 137a gripping function 137b gripping function 138 cutout part 139 projection 140 tip

Claims (15)

A button (70) for setting the dose of drug and dispensing it from the drug delivery device (1),
With a plastic component (130)
Containing a metal component (131),
Here, the plastic component (130) is at least partially received by the metal component (131) and the metal component (131) is configured to be manipulated by the user to set and dispense a dose. To be done. The metal component (131) comprises an aperture (131a) for receiving the plastic component (130), the diameter of the aperture (131a) being smaller than the maximum outer diameter of the plastic component (130),
A button (70) according to claim 1. The plastic component (130) is at least partially elastically deformable,
A button (70) according to claim 1 or 2. The metal component (131) is formed on the plastic component (130),
A button (70) according to any of the preceding claims. The metal component (131) is swaged to clamp the plastic component (130),
A button (70) according to any of the preceding claims. The metal component (131) and the plastic component (130) are non-rotatably connected to each other, the plastic component (130) comprises at least one protrusion (139) and the metal component (131) is at least one Including three cutouts (138), the protrusions (139) being received by the cutouts (138) to non-rotatably connect and / or align the plastic component (130) and the metal component (131),
A button (70) according to any of the preceding claims. The plastic component (130) comprises at least one gripping feature (137b) and the metal component (131) comprises at least one mating gripping feature (137a), said gripping features (137a, 137b) being , Applied and arranged to align the plastic component (130) and the metal component (131) when the plastic component (130) is received by the metal component (131),
A button (70) according to any one of the preceding claims. The metal component (131) is deep drawn,
A button (70) according to any one of the preceding claims. A method of assembling a button (70) of a drug delivery device (1), the button (70) comprising a plastic component (130) and a metal component (131):
Inserting the plastic component (130) at least partially into the metal component (131);
Swaging the metal component (131) to clamp the plastic component (130) to securely connect the metal component (131) and the plastic component (130).   The metal component (131) includes an aperture (131a) of a diameter large enough to receive the plastic component (130) and swaging the metal component (131) to the plastic component (130), The method according to claim 9, wherein the diameter of the aperture (131a) is reduced. When swaging the metal component (131) to the plastic component (130), the plastic component (130) is elastic such that the metal component (131) is formed on the plastic component (130) To be transformed
A method according to claim 9 or 10. The plastic component (130) includes bump features (133) disposed on the outer surface of the plastic component (130), and the metal component (131) is swaged over the bump features (133)
A method according to any one of claims 9-11.   A drug delivery device (1) comprising a button (70) according to claims 1 to 8, said drug delivery device being a reusable drug delivery device. A rotatable sleeve (62), the plastic component (130) comprising at least one ratcheting feature (132) disposed on the inner surface of the plastic component (130), the ratcheting feature (132) comprising Applied and arranged in mechanical cooperation with the sleeve (62) to provide audible feedback during delivery
14. Drug delivery device (1) according to claim 13. The drive mechanism is included and the plastic component (130) is in mechanical cooperation with the drive mechanism of the device (1) to non-rotatably and / or axially couple the button (70) and the drive mechanism. Including at least one snap function (74) applied and arranged;
The drug delivery device (1) according to claim 13 or 14.

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